AB0174 EXPLORING A POTENTIAL ANTI-TUMOR IMMUNE MICROENVIRONMENT IN GIANT CELL ARTERITIS
Authors: S. Albano-Aluquin, J. Malysz, M. Savjani, V. Aluquin, M. Ratnam, N. Olsen
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The diagnosis of giant cell arteritis (GCA) is confirmed by temporal artery (TA) biopsy findings of internal elastic lamina disruption, activated macrophages and T-lymphocytes infiltrating the arterial layers. The immune microenvironment in GCA becomes T helper-1 polarized after steroid therapy and consists of potential anti-tumor cytokines including interferon-gamma (IFG) and interleukin-12 (IL-12) which can be protective against the development of cancer. We have previously identified folate receptor beta positive macrophages in GCA, which can serve as a target for hacking this immune microenvironment. <h3>Objectives</h3> To compare the tumor outcomes in our cohort of GCA vs controls who had TA biopsies. To select a line-up of CD3, IFG, IL12 and FRB as potential anti-tumor proteins and compare their expression in GCA+ TA tissue that did not develop tumors versus GCA -negative tissues that developed tumors. To assess the persistence of this line-up over time. <h3>Methods</h3> We performed a retrospective chart review of GCA subjects and controls to assess development of tumors over long-term follow up. Formalin-fixed paraffin embedded tissue sections were obtained from both groups and immunohistochemical stains were performed using CD3, IFG, IL12 and FRB antibodies. <h3>Results</h3> 40 GCA and 40 controls demonstrated similar follow-up durations (76.9 vs 70.1 years; NS), time-to-incident cancer (21 vs 62 mos; NS) and deaths from cancer (5% vs 17.5%;NS). GCA subjects were older than controls (77.2 vs 69.7 years; p= 0.004). Cancer incidence is lower in GCA than controls (25% vs.47.5%; p=0.036). The incident cancers in GCA include 8 basal or squamous cell skin cancer(BCC/SCC) and 1 each of chronic lymphocytic leukemia, thyroid, esophageal and angiosarcoma. The controls had 6 BCC/SCC, 2 each of breast, skin melanoma and lymphoma, and 1 each of tonsil, parotid, colon, lung, renal, prostate, myelodysplastic syndrome and metastatic disease of unknown primary. Histopathology/IHC Findings: FRB was selectively expressed in macrophages and correlated with IFG, IL12 and CD3 expression. FRB, IFG, IL12 and CD3 expression were higher in GCA without incident cancer compared to controls with cancer: FRB (14 vs 2.3;p=0.006), IFG (3 vs 1;p=0.005), IL12 (1.5 vs 0;p=0.003), CD3 (79 vs 0;p=0.004). This multi- protein expression persisted for years in 3 repeat biopsies. <h3>Conclusion</h3> GCA has a lower risk of cancer which was associated with a chronic FRB+-macrophage and Th1-polarized anti-tumor autoimmunity. <h3>References</h3> [1]Deng J, Younge BR, Olshen RA, et al. Th17 and Th1 T-cell responses in giant cell arteritis. <i>Circulation</i>. 2010;121:906-915. [2]Bruni D, Angell HK, Galon J. et al. The immune contexture and immunoscore in cancer prognosis and therapeutic efficacy. <i>Nat Rev Cancer</i> 2020;20:662-680. [3]Fridman WH, Pagès F, Sautès-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. <i>Nat Rev Cancer</i>. 2012;12:298-306. [4]Smyth MJ, Taniguchi M, Street SE The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. <i>J Immunol</i> 2000;165:2665-70. [5]Albano-Aluquin S, Malysz J, Aluquin VR, et al. An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis: a pilot study. <i>Am J Clin Exp Immunol</i>. 2017;6:107-114. [6]Xia W, Hilgenbrink W, Matteson L, et al. A functional folate receptor is induced during macrophage activation can be used to target drugs to activated macrophages. <i>Blood</i> 2009;113:438-446 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.